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The influence of study characteristics on reporting of subgroup analyses in randomised controlled trials: systematic review

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1569 (Published 28 March 2011) Cite this as: BMJ 2011;342:d1569
  1. Xin Sun, research fellow 12,
  2. Matthias Briel, assistant professor13,
  3. Jason W Busse, scientist14,
  4. John J You, assistant professor 15,
  5. Elie A Akl, associate professor 16,
  6. Filip Mejza, research fellow 7,
  7. Malgorzata M Bala, research fellow 8,
  8. Dirk Bassler, associate professor 9,
  9. Dominik Mertz, research fellow 110,
  10. Natalia Diaz-Granados, doctoral candidate1,
  11. Per Olav Vandvik, researcher 1112,
  12. German Malaga, associate professor13,
  13. Sadeesh K Srinathan, assistant professor 14,
  14. Philipp Dahm, associate professor15,
  15. Bradley C Johnston, postdoctoral fellow1,
  16. Pablo Alonso-Coello, researcher 16,
  17. Basil Hassouneh, research fellow 1,
  18. Jessica Truong, undergraduate student17,
  19. Neil D Dattani, medical student18,
  20. Stephen D Walter, professor1,
  21. Diane Heels-Ansdell, statistician 1,
  22. Neera Bhatnagar, librarian 19,
  23. Douglas G Altman, professor 20,
  24. Gordon H Guyatt, professor1
  1. 1Department of Clinical Epidemiology and Biostatistics, McMaster University, 1200 Main Street, Hamilton, ON, Canada L8N 3Z5
  2. 2Chinese Evidence-Based Medicine Center, West China Hospital, Sichuan University, Chengdu, China
  3. 3Basel Institute for Clinical Epidemiology and Biostatistics, University Hospital Basel, Switzerland
  4. 4Institute for Work and Health, Toronto, ON, Canada
  5. 5Department of Medicine, McMaster University, Hamilton, ON, Canada
  6. 6Departments of Medicine and Family Medicine, State University of New York at Buffalo, NY, USA
  7. 7Department of Pulmonary Diseases, Jagiellonian University School of Medicine, Krakow, Poland
  8. 8II Department of Internal Medicine, Jagiellonian University School of Medicine, Krakow, Poland
  9. 9Department of Neonatology and Center for Pediatric Clinical Studies, University Children’s Hospital Tuebingen, Tuebingen, Germany
  10. 10Michael G DeGroote Institute for Infectious Diseases Research, McMaster University, Hamilton, ON, Canada
  11. 11Norwegian Knowledge Centre for the Health Services, Oslo, Norway
  12. 12Department of Medicine, Innlandet Hospital Trust, Gjøvik, Norway
  13. 13Universidad Peruana Cayetano Heredia, Lima, Peru
  14. 14Department of Surgery, University of Manitoba, Winnipeg, MB, Canada
  15. 15Department of Urology, College of Medicine, University of Florida, Gainesville, FL, USA
  16. 16IberoAmerican Cochrane Centre, Clinical Epidemiology and Public Health Department, Institute of Biomedical Research-CIBER of Epidemiology and Public Health, Barcelona, Spain
  17. 17Bachelor of Health Sciences Program, McMaster University, Hamilton, ON, Canada
  18. 18Doctor of Medicine Programme, University of Toronto, Toronto, ON, Canada
  19. 19Health Sciences Library, McMaster University, Hamilton, ON, Canada
  20. 20Center for Statistics in Medicine, University of Oxford, UK
  1. Correspondence to: G H Guyatt guyatt{at}mcmaster.ca
  • Accepted 24 December 2010

Abstract

Objective To investigate the impact of industry funding on reporting of subgroup analyses in randomised controlled trials.

Design Systematic review.

Data sources Medline.

Study selection Randomised controlled trials published in 118 core clinical journals (defined by the National Library of Medicine) in 2007. 1140 study reports in a 1:1 ratio by high (five general medicine journals with largest number of total citations in 2007) versus lower impact journals, were randomly sampled. Two reviewers, independently and in duplicate, used standardised, piloted forms to screen study reports for eligibility and to extract data. They also used explicit criteria to determine whether a randomised controlled trial reported subgroup analyses. Logistic regression was used to examine the association of prespecified study characteristics with reporting versus not reporting of subgroup analyses.

Results 469 randomised controlled trials were included, of which 207 (44%) reported subgroup analyses. High impact journals (adjusted odds ratio 2.64, 95% confidence interval 1.62 to 4.33), non-surgical (versus surgical) trials (2.10, 1.26 to 3.50), and larger sample size (3.38, 1.64 to 6.99) were associated with more frequent reporting of subgroup analyses. The strength of association between trial funding and reporting of subgroups differed in trials with and without statistically significant primary outcomes (interaction P=0.02). In trials without statistically significant results for the primary outcome, industry funded trials were more likely to report subgroup analyses (2.29, 1.30 to 4.72) than non-industry funded trials. This was not true for trials with a statistically significant primary outcome (0.79, 0.46 to 1.36). Industry funded trials were associated with less frequent prespecification of subgroup hypotheses (31.3% v 38.0%, adjusted odds ratio 0.49, 0.26 to 0.94), and less use of the interaction test for analyses of subgroup effects (41.4% v 49.1%, 0.52, 0.28 to 0.97) than non-industry funded trials.

Conclusion Industry funded randomised controlled trials, in the absence of statistically significant primary outcomes, are more likely to report subgroup analyses than non-industry funded trials. Industry funded trials less frequently prespecify subgroup hypotheses and less frequently test for interaction than non-industry funded trials. Subgroup analyses from industry funded trials with negative results for the primary outcome should be viewed with caution.

Footnotes

  • We thank Monica Owen for administrative assistance and Aravin Duraikannan for developing the electronic data abstraction forms.

  • Contributors: XS and GHG conceived the study, had full access to all of the data in the study, and take responsibility for the integrity of the data and the accuracy of the data analysis. GHG is the guarantor. XS, GHG, MB, JWB, EAA, SDW, DGA, and DH-A designed the study. MB, EAA, JWB, ND-G, JJY, FM, MMB, DB, DM, POV, GM, SKS, PD, BCJ, PA-C, BH, XS, JT, NDD, and NB acquired the data. XS, GHG, SDW, and DH-A analysed and interpreted the data. XS drafted the manuscript. All authors critically revised the manuscript. XS provided administrative and technical support. The funder had no role in the study design, writing of the manuscript, or the decision to submit this manuscript for publication.

  • Funding: This study was supported by the National Natural Science Foundation of China (project No 70703025). XS is supported by the Ontario graduate scholarship and the National Natural Science Foundation of China. MB is supported by santésuisse and the Gottfried and Julia Bangerter-Rhyner Foundation. JWB is funded by a new investigator award from the Canadian Institutes of Health Research and the Canadian Chiropractic Research Foundation. DB is supported by the European Union (grant award health-F5-2009-223060). DM is supported by a research scholarship from the Swiss National Science Foundation (PBBSP3-124436). PD is supported by a Dennis W Jahnigan career development award by the American Geriatrics Society. BCJ holds a SickKids Foundation post-doctoral fellowship. PA-C is funded by a Miguel Servet contract by the Instituto de Salud Carlos III (CP09/00137). JJY is supported by a career scientist award from the Ontario Ministry of Health and Long-Term Care.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: This study was supported by the National Natural Science Foundation of China (project No 70703025); no financial relationships with any organisations that might have an interest in the submitted work in the previous three years, no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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